Functional Genomic Analyses Of Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$577,001.00
Summary
Mitochondria produce most of the energy required by our bodies. Mutations in genes that make mitochondrial proteins cause mitochondrial dysfunction and lead to neurodegenerative and muscular diseases. We will identify mutations in mitochondrial genes in members of different Bulgarian and Gypsy families and discovery the mechanisms by which the mutations lead to disease.
Carolyn Sue is a neurologist and scientist investigating the role of disturbed mitochondrial function in human disease. Mitochondria play a key role in maintaining energy levels and the cell’s health. When this function is impaired, cells may degenerate or die, and thus cause human disease. Dr Sue’s research is aimed at seeking improved treatments to treat mitochondrial disease and to further understanding about how brain cells degenerate when the mitochondria fail.
Recognising And Improving Management Outcomes Of Adult Patients With Mitochondrial Diseases
Funder
National Health and Medical Research Council
Funding Amount
$87,199.00
Summary
Mitochondrial diseases comprise the most common diagnostic group amongst neuromuscular and neurogenetic diseases, but are not well known in the community, with no established standards of management. The Study aims to devise strategies to deliver better care for patients with mitochondrial diseases, from their screening and diagnosis, continued monitoring and prognostication, to the potential treatment and promotion of a better management paradigm; as well as facilitation of ongoing research int ....Mitochondrial diseases comprise the most common diagnostic group amongst neuromuscular and neurogenetic diseases, but are not well known in the community, with no established standards of management. The Study aims to devise strategies to deliver better care for patients with mitochondrial diseases, from their screening and diagnosis, continued monitoring and prognostication, to the potential treatment and promotion of a better management paradigm; as well as facilitation of ongoing research into the management of patients with these diseases.Read moreRead less
Evaluation Of Pathogenic Mechanisms Involved In Nuclear And Mitochondrial DNA-encoded Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Mitochondria produce energy for the cell. Disorders of mitochondrial function can cause human disease. These diseases are referred to as the mitochondrial disorders. Mitochondrial disorders usually involve multiple tissues, particularly the muscle and brain.These disorders are usually caused by mutations in two different types of DNA; nuclear and mitochondrial DNA. There are many forms of mitochondrial disorders; some affect young children or infants and others cause adult disease. In some cases ....Mitochondria produce energy for the cell. Disorders of mitochondrial function can cause human disease. These diseases are referred to as the mitochondrial disorders. Mitochondrial disorders usually involve multiple tissues, particularly the muscle and brain.These disorders are usually caused by mutations in two different types of DNA; nuclear and mitochondrial DNA. There are many forms of mitochondrial disorders; some affect young children or infants and others cause adult disease. In some cases, genetic defects may cause the same disease and other mutations may cause a wide range of symptoms. The reason why this occurs is unknown. This study investigates several factors that may determine why some mutations lead to a certain disease and why others may cause different diseases. These factors include the variation in energy levels that are produced by the mutant cells, and the different levels of vunerability that mutated cells may have to induced cell death. The goal of this proposal is to identify the factors that lead to mutations causing different clinical symptoms with the overall aim being to design treatment for these chronic diseases.Read moreRead less
The Role Of Molecular Chaperones And Proteases In Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Mitochondria are essential organelles providing the cell with essential molecules and being the source of oxidative energy in the cell. They are at the centre of many clinical conditions, ranging from genetic to common neurological diseases and other conditions related to ageing. We have been defining the way in which mammalian cells respond to the accumulation of unfolded proteins within the mitochondrial compartment and have found this produces what we have called the Mitochondrial Stress Resp ....Mitochondria are essential organelles providing the cell with essential molecules and being the source of oxidative energy in the cell. They are at the centre of many clinical conditions, ranging from genetic to common neurological diseases and other conditions related to ageing. We have been defining the way in which mammalian cells respond to the accumulation of unfolded proteins within the mitochondrial compartment and have found this produces what we have called the Mitochondrial Stress Response, a process that results in the selective upregulation of a suite of genes encoding mitochondrial stress proteins. This application deals with the question of the consequences to the cell of the creation of proteolytic environment. We have found that the two major proteases of the mitochondrion are upregulated and that this results in a marked increase in the rate of degradation of mitochondrial proteins. We aim to determine the specific roles of individual proteases in this process and the consequences of this proteolysis on the efflux of peptides from the mitochondria. This question has important medical implications, as one of the consequences of defects in mitochondrial function is the loss of cells from the affected tissue. We will also address the question of how mitochondrial biogenesis is regulated. We have recently found that the cytosolic molecular chaperone Hsp90 is required for protein import into mitochondria in mammalian cells. Since Hsp90 has hitherto been shown to be a key regulatory component in the steroid hormone and tyrosine kinase signalling pathways, this finding raises the possibility that protein import and thereby mitochondrial biogenesis may be regulated via the involvement of Hsp90.Read moreRead less
Mitochondrial Chaperones: Import Of Membrane-spanning Precursors Through The Inter-membrane Space
Funder
National Health and Medical Research Council
Funding Amount
$328,194.00
Summary
All cellular proteins are made on ribosomes. Highly regulated transport systems then move them about the cell. Specialised 'translocases' mediate import of proteins to the mitochondria. This project focuses on how translocase components recognise, target, and transfer their charges; in particular, on the import of a class of solute carriers that insert into the inner mitochondrial membrane.
Mitochondrial Enzyme Regulates RNA Metabolism In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$67,381.00
Summary
Mitochondria are microscopic, energy producing machines that are found in all human cells. Mitochondria contain a small set of genes that must work properly to make the energy our bodies require for health. Defects in the expression of genes coding for mitochondrial proteins causes debilitating diseases for which there are effective treatments. I will investigate how a mitochondrial protein whose dysfunction is known to cause a metabolic disease regulates mitochondrial gene expression.
Regulation Of RNA Processing In The Mitochondrial Disease MELAS
Funder
National Health and Medical Research Council
Funding Amount
$520,977.00
Summary
Mitochondria are microscopic, energy producing machines that are found in all human cells. Mitochondria contain a small set of genes that must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are currently no cures. We have developed a new set of technologies that will be applied to understand how these mutations cause disease and provide insights into possible treatments.
Regulation Of Mitochondrial Gene Expression In Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
Mitochondria are microscopic powerplants that produce most of the energy in cells. Genes that make mitochondrial proteins must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are no cures currently. A/Prof Filipovska will use new technologies to understand how these mutations cause disease and develop therapeutics for treatments of diseases caused by defects in mitochondrial genes.
The Role Of Mitochondrial Dysfunction In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$61,383.00
Summary
We have previously found that PTCD1 can regulate mitochondrial gene expression and metabolism in cells (Mercer et al., 2011 and Lopez Sanchez et al., 2011). There is still much to learn about the mitochondria and their DNA. Charactering PTCD1, a protein that has previously seen little research, will enable us to elucidate the role of this protein in mitochondria and energy metabolism in an effort to increase understanding of obesity and type 2 diabetes.